N. meningitidis is a non-motile, Gram-negative human pathogen that colonises the pharynx and causes meningitis (and, occasionally, septicaemia in the absence of meningitis). It causes both endemic and epidemic disease. Following the introduction of the conjugate vaccine against Haemophilus influenzae, N. meningitidis is the major cause of bacterial meningitis in the USA.
Based on the organism's capsular polysaccharide, various serogroups of N. meningitidis have been identified. Serogroup A is the pathogen most often implicated in epidemic disease in sub-Saharan Africa. Serogroups B and C are responsible for the vast majority of cases in the USA and in most developed, countries. Serogroups W135 and Y are responsible for the rest of the cases in the USA and developed countries. After serogroup, classification includes serotype, serosubtype and then immunotype, and the standard nomenclature lists serogroup, serotype, serosubtype, and immunotype, each separated by a colon e.g. B:4:P1.15:L3,7,9. Within serogroup B, some lineages cause disease often (hyperinvasive), some lineages cause more severe forms of disease than others (hypervirulent), and others rarely cause disease at all. Seven hypervirulent lineages are recognised, namely subgroups I, III and IV-1, ET-5 complex, ET-37 complex, A4 cluster and lineage 3. These have been defined by multilocus enzyme electrophoresis (MLEE), but multilocus sequence typing (MLST) has also been used to classify meningococci [ref. 1].
To date, vaccines against serogroup A, C, W135 and Y have used their capsular saccharides as antigens. A licensed human polysaccharide vaccine against these four serogroups has been known for many years [2,3]. More recently the focus has remained on saccharides, but the conjugation to carrier proteins. Conjugate vaccines against serogroup C have been approved for human use, and include MENJUGATE™. [4], MENINGITEC™. and NEISVACC™. Mixtures of conjugates from serogroups A+C are known [5,6] and from serogroups A+C+W135+Y have been reported [7-10].
The capsular saccharide of serogroup B cannot be used for vaccination because it is a self-antigen in humans. Chemically-modified serogroup B saccharides have been proposed [11] but have not been adopted for clinical use. Vaccines based on outer-membrane vesicles have also been tested [e.g. see ref. 34], but the protection afforded by these vaccines is typically restricted to the strain used to make the vaccine. Genome sequences for serogroups A [12] and B [13,14] have been reported, and the serogroup B sequence has been studied to identify vaccine antigens [e.g. refs. 15 to 20]. Candidate antigens have been manipulated to improve heterologous expression [refs. 21 to 23].
The established dogma for meningococcus is thus that immunisation against serogroups A, C, W135 and Y shall be based on the four different capsular saccharides, and that immunisation against serogroup B shall not be based on the capsular saccharide.